The 5A amphipathic peptide, which was shown earlier by our laboratory to be specific for removing cholesterol by the ABCA1 transporter, was tested in the past year in several animal models. Using a rabbit collar model, the 5A peptide was found to reduce the expression of adhesion molecules on endothelial cells and reduce the infiltration of inflammatory cells into the vessel wall. When mice were treated with a single IV bolus of the 5A peptide, it raised HDL-C and increased the capacity of serum for removing excess cholesterol from cells. Furthermore, the 5A peptide was found to mobilize cholesterol from peripheral tissues and increase fecal cholesterol excretion. Long term treatment of the peptide was found to markedly reduce atherosclerosis in apoE knokout mice, indicating that it may be a possible alternative to using apolipoprotein A-I for HDL infusion therapy. Structure-function studies of a family of amphipathic peptides referred to as ELK peptides revealed that certain structural motifs correlated with their in vitro biological properties. In the future, the in vitro properties of the ELK peptides will be compared to their effect on mouse models of atherosclerosis to provide a better rationale in the design of apolipoprotien mimetic peptides.